The susceptibility of the developing nervous system to environmental agents has been a major concern with regard to children's health issues. While current exposure levels to environmental agents does not represent an acute injury, disruption to the nervous system may be associated with either a structural alteration in the formation of the neural network and/or in nervous system functioning. The formation and interactions between the various cell types in the brain are critically timed events.Such windows of vulnerability is assummed to be a major component in the differential susceptibility of the developing organism to environmental insult. This project examines chemical induced perturbations during development of the nevous as indicated by various alterations in the morphology and molecular profile in the developing brain and assoicated neurobehavioral outcome of such exposure. The specific projects under study include 1) in immature mice, distribution of mercury to the brain following the intramuscular injection of various mercuricals including methylmercury, ethylmercury and the vaccine perservative, thimerosal. With methylmercury, a smaller percentage of the metal reaches the brain from an im injection versus oral delivery. Ethylmercury show less distribution to the brain than what is found with methylmercury. 2) Alterations in neuronal processes in the brain following exposure to compounds that perturb homeostatic maintenance of thyroid hormone during gestational and postnatal development. - we have confirmed alterations in the morphology of cerebellar neurons by Golgi staining in chemical-induced models of developmental hypothyroidism. 3) Inorganic lead is a known developmental neurotoxicant however, in order to examine the influence of genetic manipulations we established a mouse model of subtle lead neurotoxicity. Alterations could be seen in memory function under pharmacological challenge and by cDNA array effects were limited to a shift in transthyrethin as a potential indicator of early maturation of the blood brain barrier and chlorid plexus as a protective mechanism against a heavy metal exposure however, the consequences to such an early maturation is yet to be studied. For these studies we continue to use a number of methods to examine alterations in the developing nervous system following exposure to environmental agents including immunohistochemistry, molecular techniques to examine mRNA levels, as well as assessment of neurobehavioral functioning.